1. Fields of the Invention
The present invention relates to a radiotracer precursor and a method for preparing the same, especially to a radiotracer precursor containing a functional group of Bu3Sn and used to produce a dopamine receptor radiotracer.
2. Descriptions of Related Art
The Parkinson's disease causes a far greater burden in terms of economic and social cost to developed countries. In the people over age 65, there are about 15 percent of the people at risk of developing Parkinson's disease. Older people are even more likely to develop Parkinson's disease than younger people. The patients suffer from the loss of muscle function and mobility. Parkinson's disease has a great impact on both the sufferers and their caregiver.
The symptoms of Parkinson's disease result from the death of dopamine-generating cells in the midbrain and insufficient formation and activity of dopamine in certain neurons. Radiopharmaceuticals for imaging of dopamine receptors have been proven to be simple but powerful tools for differential diagnosis of Parkinson's and other neurodegenerative diseases. In order to diagnose diseases related to neural abnormality in the dopamine system, various radiopharmaceuticals for dopamine system imaging have been developed.
Dopamine D2/D3 receptors are distributed on dopaminergic postganglionic neurons and functioning in neurotransmission. The most common radio-imaging pharmaceuticals for binding D2/D3 receptor include 123I-IBZM(123I-iodobenzamide) or 11C-raclopride. In research of the recent decade, 123I-IBZM is widely used as a D2 receptor imaging agent. 123I-IBZM is usually used to evaluate neuro-degenerative diseases such as Parkinson's disease, Wilson's disease, Huntington's disease, etc. 123I-IBZM is the first radiopharmaceutical successfully used for imaging of D2 dopamine receptor in clinical, revealed in the paper “Dopamine D-2 Receptor Imaging Radiopharmaceuticals: Synthesis, Radiolabeling, and in Vitro Binding of (R)-(+)- and (S)-(−)-3-Iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide Journal of Medicinal Chemistry, 1988, Vol. 31, No. 5, p. 1039”, University of Pennsylvania, Kung et al., 1988. The structure of the 123I-IBZM is associated with benzamide. The 123I-IBZM is a dopamine antagonist, and is binding to the D2 receptor specifically. The 123I (iodine-123) is used in nuclear medicine imaging. There is only a very small amount of 123I-IBZM used in imaging so that the 123I-IBZM will not have pharmacological effect on users.
Refer to FIG. 1, 123I-IBZM is prepared by radioiodination of BZM [(S)-(−)-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide] with Iodine-123 in the presence of a buffer solution containing at least one oxidant. The buffer solution can be a phosphate buffer solution (pH 3) or ammonium acetate buffer solution (pH 4). The oxidant includes Chloramine T, hydrogen peroxide, and peracetic acid. However, the labeling yield and the radiochemical yield of such preparing method are unstable. Each batch has different products with great variations. This causes troubles in routine production.
Moreover, the method for preparing 123I-IBZM revealed by Kung et al has certain shortcomings. Refer to FIG. 2, it firstly produce a compound (2) by compound DMBA. Then get a compound (3) by an iodination reaction. Yet the compound (3) includes a carboxylic group. When the compound (3) is activated by thionyl chloride to form acid chloride, the carboxyl group may also react to give esters besides an amidation reaction can be carried out. Thus the yield rate is reduced. Therefore such method is not reliable.